1. Field of the Invention
The present invention relates to a cell surface protein expressed on human cortical thymocytes and its use. More particulary, the present invention relates to a novel protein (called "JL1" hereinafter) having molecular weight of about--120,000 dalton expressed exclusively on cortical thymocytes and on malignant cells of T lymphoblastic leukemia, T lymphoblastic lymphoma originated from cortical thymocytes and about 50% of all kinds of leukemia, which are identified by immunohistochemical and flow cytometric analysis, and to its diagnostic and clinical application on leukemia and T lymphoblastic lymphoma.
2. Description of Related Art
Human body shows the specific responses to foreign substances exposed after birth, and T- and B-lymphocytes and antigen presenting cells are involved in immune responses to protect human body. Lymphocytes are the major components of lymphoid organ cells and have an important role in the specific immune response during circulation through blood and lymph. The major role of B--lymphocytes is to produce antibodies against foreign substances. T lymphocytes are classified into two types, one of which has the function to help the specific immune response and the other has the function of killing cells infected by pathogens. And the role of antigen presenting cells is to engulf infecting antigens non-specifically, and to process them by cleaving into small peptides and provide their information to T lymphocytes.
Intrathymic T cell development entails complex series of proliferation, differentiation, and selection stages. T cells are originated from hematopoietic stem cells produced in embryonic liver and postnatal bone marrow. They move into thymus, differentiate, become mature, and after this, move out through blood vessel and become mature T cells. After rearrangement of T cell receptor germline gene in the thymus, thymocytes express T cell receptor complexes on their cell surfaces. The gene rearrangement process requires enzymatic system including RAG-1, RAG-2. As a result, extreme T cell receptor diversity can be produced in the course of this complicated process. However, all the T cell receptors produced cannot carry out their appropriate functions in periphery. The cells which cannot recognize the antigens provided by major histocompatibility complex (MHC) class I and class II, and cells which show strong response to self antigen are removed. These processes are called positive and negative selection, respectively. T cell receptors can accomplish their appropriate function when they recognize foreign antigen bound to their own MHC molecule on the cell surface. This educational process takes place in the thymus.
T cells express not only T cell receptors but also various cell surface proteins. These proteins are also important in T cell function. Most of these T cell surface proteins are expressed in a broad range of T cell subsets. However, some of them are expressed only at a specific stage and these proteins can be used as T cell surface markers for the determination of T cell maturation stage. Generally, the classification system by Renherz et al, using T cell surface molecules as markers, has been used for determing the differentiation stages of thymocytes. According to this classification, thymocytes are classified into (a) early thymocyte, CD4.sup.- /CD8.sup.- double negative, (b) common thymocyte, CD4.sup.+ /CD8.sup.+ double positive, and (c) mature thymocyte, CD4.sup.+ or CD8.sup.+ single positive. Early thymocytes express CD7, CD38 and CD71 proteins. They are the cells which recently arrive at the thymus from bone marrow and actively divide. The rearrangement of T cell receptor gene -TCR.beta.- occurs at this stage. Common thymocytes occupy the largest portion of the thymus and begin to express CD1, CD2, CD3, CD4, CD5, CD8 and the like on cell surfaces, and TCR.alpha. genes are rearranged. Thereafter, mature thymocytes express T cell receptors on the cell surface. Only some of them can survive and move to the next stage, and most of them die (Nikolis-Zugic, 1991, Immunol. Today, 12, 65-70). The cell surface molecules in T cells and thymocytes can be used to determine the stage of differentiation and the classification of subsets. In addition, they can be used for the diagnosis and treatment of tumors originated from T cells. These cell surface proteins have an important role in function and development of T cell.
A thymocyte should die unless its T cell receptor is appropriate. And the death is not simply a passive death but an active death requiring certain proteins or the synthesis of certain metabolic products (Rothenberg, 1990, Immunol. Today, 11, 116-119). This cell death may require the specific stimulating signals from the outside. And the cell surface proteins may be involved in the signal pathway. However, identification of cell surface molecules involved has not been possible until now. If common thymocytes express the specific proteins to transmit the signals for the selection of T cell receptor and programmed cell death, these proteins would be the intrinsic proteins at that stage. Even though a few cortical thymocyte antigens such as CD1a, b and c have been known to be expressed on thymic cortex, they are also expressed on various types of cells such as dendritic cells, brain astrocytes and B lymphocytes.